particularly during the initial phase of therapy, when the treatment is intended for

long-term intensive psychiatric care, together with laboratory facilities to monitor

optimal drug levels in plasma (Jin et al. 2010; Stout et al. 2010; Drozda et al. 2014;

Kratz and Diefenbacher 2019).

The therapeutic index [TI ¼ toxic dose/effective dose] is an important indicator

for the safety of xenobiotics. There are groups of drugs with narrow TI (e.g.,

antiepileptics, warfarin, digoxin), and even in case of antidepressants, TI has a

pivotal significance in the geriatric population, especially if co-medications are

prescribed. In two drug safety communications (2011–2012), the US-FDA

announced that co-administration of omeprazole (CYP2C19 inhibitor) with

citalopram causes abnormal heart rhythms and QT interval prolongation in geriatric

patients. As a result, maximal dose of omeprazole was restricted to 20 mg/day for

patients above 60 years. Omeprazole is a proton pump inhibitor that decreases HCl

production in the stomach and is used for treating heartburn and duodenal ulcers.

Citalopram and escitalopram are frequently prescribed in the elderly subjects, and

their interaction with omeprazole may lead to serious cardiac arrhythmias, Torsade

de Pointe and sudden cardiac arrest (Lozano et al. 2013). Patients on chronic

treatment with antidepressants should be regularly monitored for interacting drugs

mentioned in Tables 15.2 and 15.3 as well as over-the-counter medicines and newly

marketed drugs where dose adjustments may be necessary for antidepressants.

In Tables 15.2 and 15.3, we have shown examples of the safety and efficacy of

antidepressant drugs as well as the clinically relevant interactions of antidepressants

with other medications prescribed to elderly patients. The PK and PD parameters and

metabolic profiles of drugs depend up on patient’s drug metabolizing capacity, renal

and hepatic functions, pharmaceutical formulation of the drug, comorbidities, and

co-medications. Best practice to reduce the risk of drug-drug and drug-herbal

interactions requires thorough assessment of medications the patient may be taking,

and then adjust doses of medications or reduce the number of unwanted medications

accordingly. Healthcare providers should ask their elderly patients about herbal and

dietary supplement use and discourage concomitant ingestion of botanical products,

including fruit juices (grape fruit, orange, pomegranate, tomato), with pharmaceuti-

cal medications. The clinicians and pharmacists should also consider drug-disease-

interactions (especially liver and kidney disorders), and drug metabolizing capacity

of individual patients that may be unique to Caucasians, Asians, Hispanics, Blacks,

etc. and may require drug dose adjustments based on these multiple factors.

In summary, we have demonstrated via examples that special attention should be

paid to ADME of orally administered antidepressant drugs, and physiological

functions of liver and kidney should be taken into consideration while prescribing

these drugs to elderly and frail patients. Overwhelming evidence suggests that drug

dose adjustments are necessary in patients >65 years. More personalized medication

is needed compared to the actual mechanistic prescription praxis! Control of therapy

output and recognition of early signs of accidental side effects or toxic symptoms are

very important in patients with comorbidity and polymedication. Therapeutic drug

monitoring, especially in the case of narrow therapeutic index drugs, is

recommended in any uncertain situation.

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